2025-11-30
1 2 3 4 5 6
This presentation summarizes:
Last Gift Cohort
Body Donation
Autopsy
Tissue Collection
HIV Sequencing
Phylogenetics and Modeling
Image attribution: BioRender.
(click anywhere to close)
Note
Conceptual motivation
In a transition model, exposure represents the “opportunity” for observing a migration event between compartments. We considered the following definition:
\[ n_{\text{states}, i} : \text{number of Markov states in run } i \times \text{number of sequences from CNS} \times \text{number of sequences from Periphery} \]
data %>%
mutate(
pairs_cns = ntissues_cns * (ntissues_cns - 1) / 2,
pairs_periph = ntissues_periph * (ntissues_periph - 1) / 2,
exposure = case_when(
migration_type == "cross_BBB" & direction == "CNS to Periph" ~
n_states * nseq_cns * nseq_periph,
migration_type == "cross_BBB" & direction == "Periphery to CNS" ~
n_states * nseq_periph * nseq_cns,
migration_type == "within_CNS" ~
n_states * pairs_cns * (nseq_cns^2),
migration_type == "within_peripheral" ~
n_states * pairs_periph * (nseq_periph^2)
)
)
Notes
\[ \log(\mu_i) = \beta_0 + \beta_1 \cdot \text{Marker}_i + b_{\text{pid}(i)} + \log(\text{Exposure}_i) \]
fit_models <- function(marker, data_in) {
formula <- as.formula(
paste0(
"n_events ~ ", marker,
" + age + sex + last_cd4_t_cell_count + duration_infection_years +
(1 | pid) + offset(log_exposure)"
)
)
glmmTMB(
formula,
data = data_in,
family = nbinom2(),
control = glmmTMBControl(
optimizer = optim,
optArgs = list(method = "BFGS", maxit = 5000)
)
)
}
fit_models <- function(marker, data_in) {
formula <- as.formula(
paste0(
"n_events ~ ", marker,
" + age + sex + last_cd4_t_cell_count + duration_infection_years +
dna_level_from + dna_level_to +
(1 | pid) + offset(log_exposure)"
)
)
glmmTMB(
formula,
data = data_in,
family = nbinom2(),
control = glmmTMBControl(
optimizer = optim,
optArgs = list(method = "BFGS", maxit = 5000)
)
)
}
| Associations between CSF biomarkers and counts of migration events from the CNS to the periphery | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 13 | Ok | ✅ | 1.037 | 0.7983–1.35 | 0.787 | ⬆ | ||
| GM-CSF | 8 | Ok | ✅ | 0.888 | 0.7500–1.05 | 0.170 | ⬇ | ||
| GRO-alpha (CXCL1) | 13 | Ok | ✅ | 0.988 | 0.9811–1.00 | 0.001 | ** | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.154 | 0.0023–10.37 | 0.384 | ⬇ | ||
| IL-1β | 5 | Ok | ✅ | 0.805 | 0.6742–0.96 | 0.017 | * | ⬇ | |
| IL-1RA | 12 | Ok | ✅ | 1.000 | 0.9995–1.00 | 0.000 | *** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.424 | 0.2993–0.60 | 0.000 | *** | ⬇ | |
| IL-5 | 5 | Ok | ✅ | 0.986 | 0.8114–1.20 | 0.891 | ⬇ | ||
| IL-6 | 12 | NA Estimates | ❌ | 2.156 | NA–NA | NaN | ⬆ | ||
| IL-7 | 13 | Ok | ✅ | 0.351 | 0.0617–2.00 | 0.238 | ⬇ | ||
| IL-8 (CXCL8) | 13 | Ok | ✅ | 0.998 | 0.9953–1.00 | 0.047 | * | ⬇ | |
| IL-9 | 1 | Sparse Data | ❌ | 1.094 | 0.5815–2.06 | 0.781 | ⬆ | ||
| IL-10 | 8 | Ok | ✅ | 0.487 | 0.2609–0.91 | 0.024 | * | ⬇ | |
| IL-15 | 5 | Ok | ✅ | 0.459 | 0.1696–1.24 | 0.126 | ⬇ | ||
| IL-17A/CTLA-8 | 1 | Sparse Data | ❌ | 0.415 | 0.0560–3.07 | 0.389 | ⬇ | ||
| IL-18 | 13 | Ok | ✅ | 1.009 | 0.9873–1.03 | 0.434 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.930 | 0.6767–1.28 | 0.652 | ⬇ | ||
| IP-10 (CXCL10) | 13 | Ok | ✅ | 1.000 | 0.9967–1.00 | 0.828 | ⬇ | ||
| MCP-1 (CCL2) | 13 | Ok | ✅ | 1.000 | 0.9983–1.00 | 0.915 | ⬇ | ||
| MIP-1α (CCL3) | 13 | Ok | ✅ | 0.867 | 0.7731–0.97 | 0.015 | * | ⬇ | |
| MIP-1β (CCL4) | 13 | Ok | ✅ | 0.964 | 0.9421–0.99 | 0.002 | ** | ⬇ | |
| RANTES (CCL5) | 13 | Ok | ✅ | 1.007 | 0.9203–1.10 | 0.882 | ⬆ | ||
| SDF-1α | 13 | Ok | ✅ | 1.000 | 0.9993–1.00 | 0.839 | ⬆ | ||
| TNF-α | 2 | Sparse Data | ❌ | 0.333 | 0.2189–0.51 | 0.000 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events from the periphery to the CNS | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 15 | Ok | ✅ | 0.977 | 0.857–1.11 | 0.733 | ⬇ | ||
| GM-CSF | 10 | Ok | ✅ | 0.864 | 0.769–0.97 | 0.015 | * | ⬇ | |
| GRO-alpha (CXCL1) | 15 | Ok | ✅ | 0.987 | 0.981–0.99 | 0.000 | *** | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.252 | 0.013–4.88 | 0.362 | ⬇ | ||
| IL-1β | 6 | Ok | ✅ | 0.858 | 0.734–1.00 | 0.054 | . | ⬇ | |
| IL-1RA | 14 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.003 | ** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.374 | 0.301–0.47 | 0.000 | *** | ⬇ | |
| IL-5 | 7 | Ok | ✅ | 0.871 | 0.667–1.14 | 0.312 | ⬇ | ||
| IL-6 | 14 | Ok | ✅ | 0.998 | 0.997–1.00 | 0.000 | *** | ⬇ | |
| IL-7 | 15 | Ok | ✅ | 1.616 | 0.433–6.03 | 0.475 | ⬆ | ||
| IL-8 (CXCL8) | 15 | Ok | ✅ | 0.999 | 0.998–1.00 | 0.093 | . | ⬇ | |
| IL-9 | 1 | Sparse Data | ❌ | 1.201 | 0.682–2.11 | 0.526 | ⬆ | ||
| IL-10 | 9 | Ok | ✅ | 0.871 | 0.712–1.07 | 0.179 | ⬇ | ||
| IL-15 | 7 | Ok | ✅ | 0.298 | 0.143–0.62 | 0.001 | ** | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 0.725 | 0.256–2.05 | 0.544 | ⬇ | ||
| IL-18 | 15 | Ok | ✅ | 1.017 | 1.000–1.03 | 0.047 | * | ⬆ | |
| IL-31 | 1 | Sparse Data | ❌ | 0.917 | 0.701–1.20 | 0.528 | ⬇ | ||
| IP-10 (CXCL10) | 15 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.569 | ⬇ | ||
| MCP-1 (CCL2) | 15 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.881 | ⬆ | ||
| MIP-1α (CCL3) | 15 | Ok | ✅ | 0.898 | 0.831–0.97 | 0.007 | ** | ⬇ | |
| MIP-1β (CCL4) | 15 | Ok | ✅ | 0.984 | 0.967–1.00 | 0.071 | . | ⬇ | |
| RANTES (CCL5) | 15 | Ok | ✅ | 0.993 | 0.929–1.06 | 0.830 | ⬇ | ||
| SDF-1α | 15 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.272 | ⬇ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.381 | 0.234–0.62 | 0.000 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events across the BBB | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 15 | Ok | ✅ | 1.038 | 0.8740–1.23 | 0.671 | ⬆ | ||
| GM-CSF | 10 | Ok | ✅ | 0.874 | 0.7675–0.99 | 0.041 | * | ⬇ | |
| GRO-alpha (CXCL1) | 15 | Ok | ✅ | 0.989 | 0.9818–1.00 | 0.002 | ** | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.310 | 0.0072–13.34 | 0.542 | ⬇ | ||
| IL-1β | 6 | Ok | ✅ | 0.852 | 0.6821–1.07 | 0.160 | ⬇ | ||
| IL-1RA | 14 | Ok | ✅ | 1.000 | 0.9995–1.00 | 0.000 | *** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.388 | 0.3060–0.49 | 0.000 | *** | ⬇ | |
| IL-5 | 7 | Ok | ✅ | 0.918 | 0.7765–1.08 | 0.313 | ⬇ | ||
| IL-6 | 14 | Ok | ✅ | 0.998 | 0.9973–1.00 | 0.000 | *** | ⬇ | |
| IL-7 | 15 | Ok | ✅ | 1.402 | 0.3160–6.22 | 0.657 | ⬆ | ||
| IL-8 (CXCL8) | 15 | Ok | ✅ | 0.999 | 0.9970–1.00 | 0.212 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 1.129 | 0.6593–1.93 | 0.658 | ⬆ | ||
| IL-10 | 9 | Ok | ✅ | 0.872 | 0.6350–1.20 | 0.399 | ⬇ | ||
| IL-15 | 7 | Ok | ✅ | 0.319 | 0.1448–0.70 | 0.005 | ** | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 0.971 | 0.2688–3.51 | 0.964 | ⬇ | ||
| IL-18 | 15 | Ok | ✅ | 1.014 | 0.9963–1.03 | 0.119 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.965 | 0.7235–1.29 | 0.807 | ⬇ | ||
| IP-10 (CXCL10) | 15 | Ok | ✅ | 1.000 | 0.9986–1.00 | 0.715 | ⬆ | ||
| MCP-1 (CCL2) | 15 | Ok | ✅ | 1.000 | 0.9989–1.00 | 0.950 | ⬇ | ||
| MIP-1α (CCL3) | 15 | Ok | ✅ | 0.875 | 0.7832–0.98 | 0.017 | * | ⬇ | |
| MIP-1β (CCL4) | 15 | Ok | ✅ | 0.984 | 0.9608–1.01 | 0.202 | ⬇ | ||
| RANTES (CCL5) | 15 | Ok | ✅ | 1.012 | 0.9314–1.10 | 0.780 | ⬆ | ||
| SDF-1α | 15 | Ok | ✅ | 1.000 | 0.9984–1.00 | 0.963 | ⬆ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.362 | 0.2447–0.54 | 0.000 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events within CNS | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 15 | Ok | ✅ | 1.028 | 8.2e-01–1.290 | 0.810 | ⬆ | ||
| GM-CSF | 10 | Ok | ✅ | 0.892 | 7.2e-01–1.104 | 0.292 | ⬇ | ||
| GRO-alpha (CXCL1) | 15 | Ok | ✅ | 0.986 | 9.8e-01–0.997 | 0.010 | * | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.001 | 1.8e-05–0.054 | 0.001 | *** | ⬇ | |
| IL-1β | 6 | Ok | ✅ | 0.875 | 6.8e-01–1.120 | 0.289 | ⬇ | ||
| IL-1RA | 14 | Ok | ✅ | 0.999 | 1.0e+00–1.000 | 0.000 | *** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.410 | 2.4e-01–0.705 | 0.001 | ** | ⬇ | |
| IL-5 | 7 | Ok | ✅ | 1.207 | 8.2e-01–1.769 | 0.334 | ⬆ | ||
| IL-6 | 14 | Ok | ✅ | 0.998 | 1.0e+00–1.000 | 0.044 | * | ⬇ | |
| IL-7 | 15 | Ok | ✅ | 0.362 | 8.1e-02–1.629 | 0.186 | ⬇ | ||
| IL-8 (CXCL8) | 15 | Ok | ✅ | 0.999 | 1.0e+00–1.002 | 0.507 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 0.560 | 2.6e-01–1.217 | 0.143 | ⬇ | ||
| IL-10 | 9 | Ok | ✅ | 1.004 | 7.0e-01–1.434 | 0.983 | ⬆ | ||
| IL-15 | 7 | Ok | ✅ | 0.231 | 6.2e-02–0.861 | 0.029 | * | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 1.644 | 2.4e-01–11.447 | 0.616 | ⬆ | ||
| IL-18 | 15 | Ok | ✅ | 1.013 | 9.8e-01–1.043 | 0.376 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.881 | 6.4e-01–1.213 | 0.437 | ⬇ | ||
| IP-10 (CXCL10) | 15 | Ok | ✅ | 1.000 | 9.9e-01–1.006 | 0.968 | ⬆ | ||
| MCP-1 (CCL2) | 15 | Ok | ✅ | 0.999 | 1.0e+00–1.001 | 0.236 | ⬇ | ||
| MIP-1α (CCL3) | 15 | Ok | ✅ | 0.915 | 8.0e-01–1.046 | 0.191 | ⬇ | ||
| MIP-1β (CCL4) | 15 | Ok | ✅ | 0.971 | 9.4e-01–1.007 | 0.117 | ⬇ | ||
| RANTES (CCL5) | 15 | Ok | ✅ | 0.914 | 8.1e-01–1.032 | 0.145 | ⬇ | ||
| SDF-1α | 15 | Ok | ✅ | 1.000 | 1.0e+00–1.001 | 0.663 | ⬇ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.446 | 2.0e-01–1.003 | 0.051 | . | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events from the CNS to the periphery | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 13 | Ok | ✅ | 1.043 | 0.921–1.18 | 0.507 | ⬆ | ||
| GM-CSF | 8 | Ok | ✅ | 0.927 | 0.859–1.00 | 0.049 | * | ⬇ | |
| GRO-alpha (CXCL1) | 13 | Ok | ✅ | 0.996 | 0.992–1.00 | 0.047 | * | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.077 | 0.014–0.42 | 0.003 | ** | ⬇ | |
| IL-1β | 5 | Ok | ✅ | 0.962 | 0.841–1.10 | 0.567 | ⬇ | ||
| IL-1RA | 12 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.000 | *** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.701 | 0.545–0.90 | 0.006 | ** | ⬇ | |
| IL-5 | 5 | Ok | ✅ | 0.975 | 0.890–1.07 | 0.596 | ⬇ | ||
| IL-6 | 12 | Ok | ✅ | 0.999 | 0.999–1.00 | 0.018 | * | ⬇ | |
| IL-7 | 13 | Ok | ✅ | 1.521 | 0.600–3.86 | 0.377 | ⬆ | ||
| IL-8 (CXCL8) | 13 | Ok | ✅ | 0.998 | 0.996–1.00 | 0.061 | . | ⬇ | |
| IL-9 | 1 | Sparse Data | ❌ | 0.769 | 0.550–1.08 | 0.125 | ⬇ | ||
| IL-10 | 8 | Ok | ✅ | 0.598 | 0.453–0.79 | 0.000 | *** | ⬇ | |
| IL-15 | 5 | Ok | ✅ | 0.763 | 0.464–1.25 | 0.285 | ⬇ | ||
| IL-17A/CTLA-8 | 1 | Sparse Data | ❌ | 0.712 | 0.262–1.93 | 0.504 | ⬇ | ||
| IL-18 | 13 | Ok | ✅ | 1.009 | 0.998–1.02 | 0.107 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 1.023 | 0.868–1.21 | 0.786 | ⬆ | ||
| IP-10 (CXCL10) | 13 | Ok | ✅ | 1.000 | 0.998–1.00 | 0.785 | ⬇ | ||
| MCP-1 (CCL2) | 13 | Ok | ✅ | 0.999 | 0.999–1.00 | 0.000 | *** | ⬇ | |
| MIP-1α (CCL3) | 13 | Ok | ✅ | 0.952 | 0.885–1.02 | 0.179 | ⬇ | ||
| MIP-1β (CCL4) | 13 | Ok | ✅ | 0.982 | 0.968–1.00 | 0.010 | ** | ⬇ | |
| RANTES (CCL5) | 13 | Ok | ✅ | 1.000 | 0.958–1.04 | 0.987 | ⬆ | ||
| SDF-1α | 13 | Ok | ✅ | 1.000 | 0.998–1.00 | 0.882 | ⬇ | ||
| TNF-α | 2 | Sparse Data | ❌ | 0.610 | 0.464–0.80 | 0.000 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events from the periphery to the CNS | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 14 | Ok | ✅ | 1.030 | 0.921–1.15 | 0.608 | ⬆ | ||
| GM-CSF | 9 | Ok | ✅ | 0.922 | 0.850–1.00 | 0.051 | . | ⬇ | |
| GRO-alpha (CXCL1) | 14 | Ok | ✅ | 0.995 | 0.990–1.00 | 0.028 | * | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.927 | 0.076–11.28 | 0.953 | ⬇ | ||
| IL-1β | 6 | Ok | ✅ | 0.897 | 0.775–1.04 | 0.149 | ⬇ | ||
| IL-1RA | 13 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.059 | . | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.589 | 0.475–0.73 | 0.000 | *** | ⬇ | |
| IL-5 | 6 | Ok | ✅ | 0.960 | 0.863–1.07 | 0.444 | ⬇ | ||
| IL-6 | 13 | Ok | ✅ | 0.999 | 0.998–1.00 | 0.039 | * | ⬇ | |
| IL-7 | 14 | Ok | ✅ | 1.251 | 0.425–3.69 | 0.685 | ⬆ | ||
| IL-8 (CXCL8) | 14 | Ok | ✅ | 1.000 | 0.998–1.00 | 0.444 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 1.138 | 0.795–1.63 | 0.480 | ⬆ | ||
| IL-10 | 9 | Ok | ✅ | 0.895 | 0.717–1.12 | 0.328 | ⬇ | ||
| IL-15 | 6 | Ok | ✅ | 0.500 | 0.326–0.77 | 0.002 | ** | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 1.002 | 0.422–2.38 | 0.996 | ⬆ | ||
| IL-18 | 14 | Ok | ✅ | 1.008 | 0.997–1.02 | 0.150 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.951 | 0.792–1.14 | 0.589 | ⬇ | ||
| IP-10 (CXCL10) | 14 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.803 | ⬆ | ||
| MCP-1 (CCL2) | 14 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.727 | ⬆ | ||
| MIP-1α (CCL3) | 14 | Ok | ✅ | 0.915 | 0.848–0.99 | 0.020 | * | ⬇ | |
| MIP-1β (CCL4) | 14 | Ok | ✅ | 0.991 | 0.975–1.01 | 0.286 | ⬇ | ||
| RANTES (CCL5) | 14 | Ok | ✅ | 1.007 | 0.957–1.06 | 0.783 | ⬆ | ||
| SDF-1α | 14 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.895 | ⬇ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.565 | 0.403–0.79 | 0.001 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events across the BBB | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 14 | Ok | ✅ | 1.026 | 0.924–1.14 | 0.634 | ⬆ | ||
| GM-CSF | 9 | Ok | ✅ | 0.928 | 0.861–1.00 | 0.054 | . | ⬇ | |
| GRO-alpha (CXCL1) | 14 | Ok | ✅ | 0.995 | 0.991–1.00 | 0.033 | * | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.553 | 0.057–5.32 | 0.608 | ⬇ | ||
| IL-1β | 6 | Ok | ✅ | 0.905 | 0.791–1.04 | 0.149 | ⬇ | ||
| IL-1RA | 13 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.009 | ** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.612 | 0.498–0.75 | 0.000 | *** | ⬇ | |
| IL-5 | 6 | Ok | ✅ | 0.969 | 0.877–1.07 | 0.529 | ⬇ | ||
| IL-6 | 13 | Ok | ✅ | 0.999 | 0.999–1.00 | 0.034 | * | ⬇ | |
| IL-7 | 14 | Ok | ✅ | 1.263 | 0.464–3.43 | 0.648 | ⬆ | ||
| IL-8 (CXCL8) | 14 | Ok | ✅ | 0.999 | 0.998–1.00 | 0.246 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 1.076 | 0.772–1.50 | 0.666 | ⬆ | ||
| IL-10 | 9 | Ok | ✅ | 0.882 | 0.723–1.08 | 0.220 | ⬇ | ||
| IL-15 | 6 | Ok | ✅ | 0.557 | 0.357–0.87 | 0.010 | ** | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 0.916 | 0.414–2.03 | 0.829 | ⬇ | ||
| IL-18 | 14 | Ok | ✅ | 1.008 | 0.997–1.02 | 0.153 | ⬆ | ||
| IL-31 | 1 | Sparse Data | ❌ | 0.958 | 0.809–1.13 | 0.614 | ⬇ | ||
| IP-10 (CXCL10) | 14 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.897 | ⬆ | ||
| MCP-1 (CCL2) | 14 | Ok | ✅ | 1.000 | 0.999–1.00 | 0.984 | ⬆ | ||
| MIP-1α (CCL3) | 14 | Ok | ✅ | 0.920 | 0.859–0.98 | 0.017 | * | ⬇ | |
| MIP-1β (CCL4) | 14 | Ok | ✅ | 0.989 | 0.975–1.00 | 0.149 | ⬇ | ||
| RANTES (CCL5) | 14 | Ok | ✅ | 1.007 | 0.960–1.06 | 0.778 | ⬆ | ||
| SDF-1α | 14 | Ok | ✅ | 1.000 | 1.000–1.00 | 0.837 | ⬇ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.583 | 0.434–0.78 | 0.000 | *** | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between CSF biomarkers and counts of migration events within CNS | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | |||||||||
| Marker | Samples Detectable1 | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| Eotaxin (CCL11) | 15 | Ok | ✅ | 1.319 | 0.91–1.91 | 0.141 | ⬆ | ||
| GM-CSF | 10 | Ok | ✅ | 0.721 | 0.35–1.47 | 0.369 | ⬇ | ||
| GRO-alpha (CXCL1) | 15 | Ok | ✅ | 0.534 | 0.28–1.01 | 0.054 | . | ⬇ | |
| IL-1α | 1 | Sparse Data | ❌ | 0.662 | 0.51–0.86 | 0.003 | ** | ⬇ | |
| IL-1β | 6 | Ok | ✅ | 0.965 | 0.52–1.78 | 0.909 | ⬇ | ||
| IL-1RA | 14 | Ok | ✅ | 0.471 | 0.32–0.68 | 0.000 | *** | ⬇ | |
| IL-2 | 2 | Sparse Data | ❌ | 0.572 | 0.36–0.90 | 0.015 | * | ⬇ | |
| IL-5 | 7 | Ok | ✅ | 0.831 | 0.39–1.77 | 0.631 | ⬇ | ||
| IL-6 | 14 | Ok | ✅ | 0.510 | 0.28–0.93 | 0.027 | * | ⬇ | |
| IL-7 | 15 | Ok | ✅ | 1.186 | 0.73–1.92 | 0.488 | ⬆ | ||
| IL-8 (CXCL8) | 15 | Ok | ✅ | 0.785 | 0.53–1.16 | 0.227 | ⬇ | ||
| IL-9 | 1 | Sparse Data | ❌ | 0.630 | 0.46–0.86 | 0.003 | ** | ⬇ | |
| IL-10 | 9 | Ok | ✅ | 1.071 | 0.68–1.69 | 0.769 | ⬆ | ||
| IL-15 | 7 | Ok | ✅ | 0.657 | 0.43–1.01 | 0.055 | . | ⬇ | |
| IL-17A/CTLA-8 | 2 | Sparse Data | ❌ | 1.268 | 0.88–1.84 | 0.209 | ⬆ | ||
| IL-18 | 15 | Ok | ✅ | 1.673 | 0.95–2.96 | 0.077 | . | ⬆ | |
| IL-31 | 1 | Sparse Data | ❌ | 1.164 | 0.65–2.10 | 0.613 | ⬆ | ||
| IP-10 (CXCL10) | 15 | Ok | ✅ | 1.200 | 0.86–1.68 | 0.286 | ⬆ | ||
| MCP-1 (CCL2) | 15 | Ok | ✅ | 0.492 | 0.30–0.82 | 0.006 | ** | ⬇ | |
| MIP-1α (CCL3) | 15 | Ok | ✅ | 0.827 | 0.45–1.52 | 0.541 | ⬇ | ||
| MIP-1β (CCL4) | 15 | Ok | ✅ | 0.877 | 0.59–1.30 | 0.513 | ⬇ | ||
| RANTES (CCL5) | 15 | Ok | ✅ | 1.001 | 0.67–1.50 | 0.996 | ⬆ | ||
| SDF-1α | 15 | Ok | ✅ | 1.023 | 0.62–1.68 | 0.929 | ⬆ | ||
| TNF-α | 3 | Sparse Data | ❌ | 0.558 | 0.32–0.97 | 0.038 | * | ⬇ | |
| 1 Number of samples with ≥1 measure(s) above the LOD across the 3 replicates. | |||||||||
| Associations between Reservoirs Measures and counts of migration events from the CNS to the periphery | ||||||||
|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | ||||||||
| Reservoir Measures | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| HIV DNA (source) | Ok | ✅ | 0.914 | 7.4e-01–1.1e+00 | 0.414 | ⬇ | ||
| HIV DNA (destination) | Ok | ✅ | 1.005 | 8.5e-01–1.2e+00 | 0.954 | ⬆ | ||
| Viral Diversity (source) | Ok | ✅ | >1e6 | 5.6e+04–+Inf | 0.006 | ** | ⬆ | |
| Viral Diversity (destination) | Ok | ✅ | >1e6 | 5.4e-02–+Inf | 0.096 | . | ⬆ | |
| Viral Divergence | Wide CI | ❌ | 3.318 | <1e-6–+Inf | 0.917 | ⬆ | ||
| Associations between Reservoirs Measures and counts of migration events from the periphery to the CNS | ||||||||
|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | ||||||||
| Reservoir Measures | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| HIV DNA (source) | Ok | ✅ | 1.147 | 1.0e+00–1.3e+00 | 0.046 | * | ⬆ | |
| HIV DNA (destination) | Ok | ✅ | 0.974 | 8.5e-01–1.1e+00 | 0.702 | ⬇ | ||
| Viral Diversity (source) | Ok | ✅ | >1e6 | 9.5e-01–+Inf | 0.051 | . | ⬆ | |
| Viral Diversity (destination) | Wide CI | ❌ | 0.054 | <1e-6–+Inf | 0.739 | ⬇ | ||
| Viral Divergence | Wide CI | ❌ | 0.002 | <1e-6–+Inf | 0.558 | ⬇ | ||
| Associations between Reservoirs Measures and counts of migration events across the BBB | ||||||||
|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | ||||||||
| Reservoir Measures | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| HIV DNA (source) | Ok | ✅ | 1.163 | 1.1e+00–1.3e+00 | 0.002 | ** | ⬆ | |
| HIV DNA (destination) | Ok | ✅ | 0.929 | 8.5e-01–1.0e+00 | 0.109 | ⬇ | ||
| Viral Diversity (source) | Ok | ✅ | >1e6 | 3.5e+04–+Inf | 0.000 | *** | ⬆ | |
| Viral Diversity (destination) | Ok | ✅ | 0.7 | 1.1e-06–4.3e+05 | 0.958 | ⬇ | ||
| Viral Divergence | Ok | ✅ | 0.015 | <1e-6–4.2e+05 | 0.633 | ⬇ | ||
| Associations between Reservoirs Measures and counts of migration events within CNS | ||||||||
|---|---|---|---|---|---|---|---|---|
| Negative Binomial Models (per transition) | ||||||||
| Reservoir Measures | Effect | Status | exp(Beta) | 95% CI | p-value | Significance | Direction | |
| HIV DNA (source) | Ok | ✅ | 0.732 | 6.3e-01–8.5e-01 | 0.000 | *** | ⬇ | |
| HIV DNA (destination) | Ok | ✅ | 1.061 | 9.4e-01–1.2e+00 | 0.345 | ⬆ | ||
| Viral Diversity (source) | Wide CI | ❌ | 140.794 | <1e-6–+Inf | 0.622 | ⬆ | ||
| Viral Diversity (destination) | Ok | ✅ | 37130.097 | 2.5e-03–+Inf | 0.212 | ⬆ | ||
| Viral Divergence | Wide CI | ❌ | 4.294 | <1e-6–+Inf | 0.884 | ⬆ | ||
Note
| 🧠 Last Gift cohort HIV Reservoir CNS Clusters | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| cluster1 | Cluster size | tMRCA (median) | lower HPD | upper HPD | Basal Ganglia | Frontal Cortex (motor) | Hippocampus | Occipital Cortex | Spinal Cord (cervical) | Spinal Cord (lumbosacral) | Spinal Cord (thoracic) | Pons | Medulla |
| LG03 | |||||||||||||
| Cluster 1 | 17 | 2005-10-26 | 1995-11-01 | 2011-12-05 | 4 (24%) | 1 (6%) | 2 (12%) | 1 (6%) | 3 (18%) | 3 (18%) | 3 (18%) | – | – |
| LG05 | |||||||||||||
| Cluster 1 | 17 | 2015-09-14 | 2012-10-21 | 2017-05-04 | 6 (35%) | 5 (29%) | 1 (6%) | 1 (6%) | – | – | – | 4 (24%) | – |
| LG14 | |||||||||||||
| Cluster 1 | 21 | 2014-06-04 | 2012-01-08 | 2016-03-26 | 7 (33%) | – | – | – | 5 (24%) | 4 (19%) | – | 5 (24%) | – |
| LG16 | |||||||||||||
| Cluster 1 | 12 | 2012-10-05 | 2002-03-02 | 2017-05-15 | – | – | – | – | – | – | – | 7 (58%) | 5 (42%) |
| LG18 | |||||||||||||
| Cluster 1 | 6 | 2006-01-15 | 1997-03-12 | 2013-06-26 | – | – | – | – | – | – | – | – | 6 (100%) |
| 1 Using most recently single genome sequencing env data | |||||||||||||
HIV Persistence & Dynamics | Research Presentation